The main purpose of this study is to assess metabolic effects of non-nutritive sweeteners, focusing on sucralose and acesulfame-potassium. In a previous pilot study, we observed that diet soda (Diet Rite Cola) augments glucose-stimulated GLP-1 secretion in young, healthy volunteers. Subjects 12 to 25 years of age participated in two 75 gram oral glucose tolerance tests (OGTT) on separate days. Ten minutes prior to the glucose load, subjects drank 240 mL of either caffeine-free diet soda (Diet Rite cola) sweetened with sucralose and acesulfame-potassium, or unflavored carbonated water, in randomized order, with each subject serving as his/her own control. Glucose, insulin, and GLP-1 were measured for 180 minutes after the glucose load. This study showed a higher GLP-1 peak and area under the curve in the diet soda condition, with no significant alteration in either plasma glucose or insulin. GLP-1 has several well-known metabolic effects. It is an incretin hormone, which augments glucose-dependent insulin secretion in response to oral nutrients. In addition GLP-1 slows gastric emptying and increases satiety. All of these effects have been exploited in patients with type 2 diabetes, in whom exogenous GLP-1 analogues result in improved glycemia control and weight loss. The main physiologic effects of endogenous GLP-1 at the plasma levels observed in our prior study, peaking at approximately 21 pg/ml, are not known. When exogenous GLP-1 was given at doses resulting in 4-10 fold higher plasma levels, the primary effect appeared to be slower gastric emptying. Plasma insulin levels in this experiment were not increased, suggesting that the incretin effect may not be prominent at such plasma levels. In the presently ongoing study, the first subject was recruited in November 2010. One hundred and two subjects have been enrolled so far (49 in the first part of the study, in which we tested sucralose alone and 53 in the second part of the study, in which participants ingest either diet sodas or a combination of sucralose and acesulfame-potassium. An interim analysis showed no difference in GLP-1 secretion in response to a glucose load, preceded by sucralose alone compared to a plain water control. Based on these results we proceeded to the second part of the study in which we use combinations of non-nutritive sweeteners. In addition to confirming our prior findings using the same Diet Rite Cola used in our pilot study, we are testing an additional commercially-available soda to assess another combination of non-nutritive sweeteners. In addition to the Diet Rite Cola, sweetened with 68 mg sucralose and 41 mg acesulfame potassium, we are now testing two other solutions, containing the same two sweeteners but with different formulations. These additional two beverages are 1) 68 mg sucralose and 41 mg acesulfame potassium (same concentrations as in Diet Rite Cola) dissolved in water and 2) an identical volume of a different commercially prepared diet soda, Caffeine Free Diet Mountain Dew, sweetened with sucralose, acesulfame-potassium and aspartame. Additionally, we are measuring GLP-1 in saliva and we are testing the effects of the sweet taste receptor inhibitor lactisole on GLP-1 secretion. Thus far, saliva has been collected in 8 subjects. No participant has been enrolled in the lactisole arm to date.